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Generation of an allele to inactivate Wnt4 gene function conditionally in the mouse
Author(s) -
Shan Jingdong,
Jokela Tiina,
Peltoketo Hellevi,
Vainio Seppo
Publication year - 2009
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20566
Subject(s) - wnt4 , biology , wnt signaling pathway , allele , cre recombinase , conditional gene knockout , genetics , fate mapping , transgene , microbiology and biotechnology , genetically modified mouse , gene , embryonic stem cell , phenotype
The Wnt family member Wnt4 is critical for the development of several organs, including the kidney, gonad, and adrenal, mammary, and pituitary glands. To study its potential postnatal functions, we generated a floxed Wnt4 allele. A single loxP site was targeted to the second intron, while a loxP‐Neo‐loxP cassette was placed 3′ from Exon 5. The floxed Neo cassette was subsequently removed by crossing with MeuCre40 transgenic mice. The Wnt4 gene was specifically inactivated with CAGCre and another Wnt4 allele, Wnt4 EGFPCre , in which the Cre is driven by the endogenous Wnt4 promoter. Deletion of Wnt4 gene function with CAGCre impaired kidney development, as is the case with the conventional knockout. Similarly, the Wnt4 EGFPCre ‐mediated inactivation of Wnt4 function considerably reduced the amount of Wnt4 transcripts, led to a severe defect in kidney development, and caused the female embryos to undergo partial sex reversal to males. All in all, the floxed Wnt4 allele serves as a useful tool for studying the roles of Wnt4 signaling during the life cycle. genesis 47:782–788, 2009. © 2009 Wiley‐Liss, Inc.